Biology subjects

Yoshinaga, M. Y.

Publications and source records attributed to Yoshinaga, M. Y..

3 recordsLinked to original sources

bioRxiv2021

Calorie Restriction Maintains Mitochondrial Function and Redox Balance Avoiding Lipidomic Reprogramming during Isoproterenol-Induced Cardiac Hypertrophy

Cardiac hypertrophy induces a metabolic shift, leading to a preferential consumption of glucose (over fatty acids) to support the high energetic demand. Typically, health cardiac tissue utilizes more fat than any other organ. Calorie restriction is a dietary procedure that induces health benefits and lifespan extension in many organisms. Given the beneficial effects of calorie restriction and the metabolic dysregulation seen during cardiac hypertrophy, we hypothesized that calorie restriction prevents cardiac hypertrophy, lipid, mitochondrial, and redox dysregulations. Strikingly, calorie restriction reversed isoproterenol-induced cardiac hypertrophy, lowered succinate driven mitochondrial H2O2 production, improved mitochondrial function (indicated as a higher Respiratory Control Ratio - RCR) and avoided mitochondrial superoxide dismutase (MnSOD) and glutathione peroxidase (GPX) repression. To gain insight into how calorie restriction could interfere with the metabolic changes induced by cardiac hypertrophy, we performed lipidomic profiling. Calorie restriction protected against the consumption of several triglycerides (TG) linked to unsaturated fatty acids, and the accumulation of TGs containing saturated fatty acids observed in hypertrophic samples. Cardiac hypertrophy induced an increase in ceramides, phosphoethanolamines and acylcarnitines (12:0, 14:0, 16:0 and 18:0) that were also reversed by calorie restriction. Altogether, our data demonstrate that hypertrophy changes the cardiac lipidome, causes mitochondrial disturbances and oxidative stress. All these changes are prevented by calorie restriction intervention in vivo. This study uncovers calorie restriction as a resource protect cardiac tissue and prevent cardiac hypertrophy-induced lipidomic remodeling.

biochemistry↗

bioRxiv2021

Resource sharing by outer membrane vesicles from a citrus pathogen

The causative agent of citrus canker disease, Xanthomonas citri pv. citri, was found to produce copious amounts of outer membrane vesicles (OMVs), frequently forming long membranous tubes under different culture conditions. Lipidomic analysis revealed significant differences in lipid composition between purified vesicles in relation to whole cells. The results suggest an enrichment in saturated cardiolipins and a decrease in unsaturated lipids in the OMV samples, possibly granting them a more rigid structure while allowing their high degree of curvature caused by their small diameters. The vesicles proteome was found to be significantly enriched in TonB-dependent receptors related to the acquisition of different nutrients. These proteins are known to transport siderophores, which were evidenced to be present in purified X. citri OMVs, along with essential metals including iron, zinc, and manganese quantified by elemental analysis. The availability of vesicle-associated nutrients to be incorporated by cells was demonstrated by the use of OMVs as the sole carbon source for bacterial growth. At last, the vesicles also presented esterase and protease activities, which have been associated with virulence in phytopathogens. These evidences point that X. citri cells can use OMVs to share resources within microbial communities, which has potential implications for microbial interactions and plant colonization, affecting their survival and persistence on the host and in the environment. ImportanceThe shedding of outer membrane vesicles appears to be universal in Gram-negative bacteria and effectively constitutes a unique secretion pathway for diverse molecules and proteins. To study their possible functions in the citrus pathogen Xanthomonas citri, purified vesicles from this bacterium were studied by omics and functional approaches. Nutrient transporters were found associated to these structures, which were evidenced to contain siderophores and essential metals. The availability of these nutrients to be incorporated by cells was then demonstrated by showing that purified vesicles can be used as sole carbon sources for microbial growth. Additionally, the samples also presented esterase and protease activities which can contribute to the release of substrates from plant host tissues. These observations help to establish the developing idea of vesicles as shared bacterial resources which can participate in shaping host-associated microbial communities in contrast to other interactions such as bacterial competition.

microbiology↗

bioRxiv2020

Distinct photooxidation-induced cell death pathways lead to selective killing of human breast cancer cells

Lack of effective treatments for aggressive breast cancer is still a major global health problem. We previously reported that Photodynamic Therapy using Methylene Blue as photosensitizer (MB-PDT) massively kills metastatic human breast cancer, marginally affecting healthy cells. In this study we aimed to unveil the molecular mechanisms behind MB-PDT effectiveness. Through lipidomic and biochemical approaches we demonstrated that MB-PDT efficiency and specificity relies on polyunsaturated fatty acids-enriched membranes and on the better capacity to deal with photooxidative damage displayed by non-tumorigenic cells. We found out that, in tumorigenic cells, lysosome membrane permeabilization is accompanied by ferroptosis and/or necroptosis. Our results broadened the understanding of MB-PDT-induced photooxidation mechanisms and specificity in breast cancer cells. Therefore, we demonstrated that efficient approaches could be designed on the basis of lipid composition and metabolic features for hard-to-treat cancers. The results further reinforce MB-PDT as a therapeutic strategy for highly aggressive human breast cancer cells.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗